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• W3026494485 abstract "Asthma or asthma-like disease is highly prevalent in children born prematurely; however, it lacks the typical features of high rates of atopy or family history that characterize childhood asthma.1Halvorsen T. Skadberg B.T. Eide G.E. Roksund O. Aksnes L. Oymar K. Characteristics of asthma and airway hyper-responsiveness after premature birth.Pediatr Allergy Immunol. 2005; 16: 487-494Crossref PubMed Scopus (94) Google Scholar Furthermore, aside from exposure to tobacco smoke,2Palta M. Sadek-Badawi M. Sheehy M. et al.Respiratory symptoms at age 8 years in a cohort of very low birth weight children.Am J Epidemiol. 2001; 154: 521-529Crossref PubMed Scopus (84) Google Scholar little is known about how premature children with asthma may react to typical environmental triggers for asthma. A study by Strickland et al3Strickland M.J. Klein M. Flanders W.D. et al.Modification of the effect of ambient air pollution on pediatric asthma emergency visits: susceptible subpopulations.Epidemiology. 2014; 25: 843-850Crossref PubMed Scopus (40) Google Scholar found ambient air pollution exposure differentially led to asthma morbidity in children born prematurely. We previously found that classroom exposure to nitrogen dioxide (NO2) was associated with increased airflow obstruction in school-aged children with asthma in the School Inner City Asthma Study (SICAS).4Gaffin J.M. Hauptman M. Petty C.R. et al.Nitrogen dioxide exposure in school classrooms of inner-city children with asthma.J Allergy Clin Immunol. 2018; 141: 2249-2255.e2Abstract Full Text Full Text PDF PubMed Scopus (59) Google Scholar Here, we further aimed to test the hypothesis that exposure to poor indoor air quality disproportionately affects asthma morbidity in children born prematurely. The School Inner City Asthma Study (SICAS) is a longitudinal study of indoor allergens and pollutants measured twice during the academic year in inner city schools in the northeastern United States.5Phipatanakul W. Bailey A. Hoffman E.B. et al.The school inner-city asthma study: design, methods, and lessons learned.J Asthma. 2011; 48: 1007-1014Crossref PubMed Scopus (55) Google Scholar Briefly, school children with asthma were enrolled in the summer, and weeklong NO2, particulate matter < 2.5 μm (PM2.5), and black carbon (BC) were measured twice during the school year, in fall and spring seasons, in school classrooms attended by enrolled students. Boston Children’s Hospital investigational review board approved this study and all subjects provided consent for research. Asthma symptom days, assessed as the greatest number of days with nighttime or daytime symptoms or activity limitation in a 14-day recall, were collected quarterly, and spirometry was performed twice annually around the time of environmental exposure collection. For the current analysis, we evaluated the interaction of preterm birth (determined by parental questionnaire response to the child being born > 3 weeks early) with pollution exposure (continuous predictor) on asthma symptoms (maximum number of days or nights with asthma symptoms or limited activity because of asthma in the 14 days prior to survey), and secondarily on health-care utilization (number of unscheduled asthma clinical visits) and spirometry outcomes. The exposure-outcome relationship was evaluated for each pollutant individually using generalized estimating equations with an exchangeable correlation structure and robust variance estimates, with clustering defined at the participant level. Season may affect pollutants and health outcomes in asthma. Therefore, all models included linear and quadratic terms for the number of days since school started to address the seasonality of asthma activity across the study period. Symptom outcomes were adjusted for age, race, sex, and tobacco smoke exposure because of a priori assumptions that these may be important confounders. Binomial family generalized estimating equations with a logit link and an overdispersion parameter were used for 2-week outcomes (ie, 2-week outcomes were modeled as the sum of 14 binomial successes). Spirometry was modeled using Gaussian family and identity link, and health-care utilization was modeled using negative binomial family and log link. Demographic characteristics of the 47 preterm children were similar to the 250 term children with asthma; however, preterm children had a significantly greater number of baseline asthma symptom days (4.3 ± 4.8 vs 2.9 ± 4.2 days, respectively; P = .03) and lower FVC (95.3 ± 18.1 vs 101.5 ± 17.0, respectively; P = .04) (Table 1). Notably, there was no difference in allergic sensitization. Median values for classroom NO2, PM2.5, and BC were 10.4 parts per billion (interquartile range, 8.0-12.9), 4.9 μg/m3 (interquartile range, 3.7-6.1), and 0.25 μg/m3 (interquartile range, 0.13-0.38), respectively. After adjustment for age, race, sex, tobacco smoke exposure, and seasonality, we found the effect of BC (every 0.1 μg/m3 increase) on maximum asthma symptom days was greater in the preterm group than the term group (OR, 1.29; 95% CI, 1.02-1.64 vs OR, 0.92; 95% CI, 0.81-1.04, respectively; interaction P = .01) (Fig 1). Similarly, there was a significantly lower FEV1 % predicted in preterm children than term children with exposure to PM2.5 (β coefficient per 1 μg/m3 increase, −1.0; 95% CI, −2.3 to 0.2 vs 0.6; 95% CI, −0.2 to 1.5, respectively; interaction P = .02). There were no significant interactions between preterm birth and NO2 exposure on health outcomes and no interactions between preterm and any exposure on health-care utilization.Table 1Baseline Characteristics of Children Enrolled in the School Inner City Asthma Study by Premature vs Term BirthCharacteristicsPremature Birth (n = 47)Term Birth (n = 250)P ValueAge, y7.4 ± 1.98.0 ± 1.9.08Male28 (60)128 (51).29Race.56 White2 (4)12 (5) Black19 (40)84 (34) Hispanic/Latino18 (38)88 (35) Multiracial7 (15)45 (18) Other1 (2)21 (8)< $25,000 household income14 (38)114 (53).08Tobacco smoke exposure15 (32)82 (33).91FVC, %95.3 ± 18.1101.5 ± 17.0.04FEV1, %98.5 ± 17.3102.1 ± 18.5.26FEV1/FVC0.88 ± 0.070.87 ± 0.07.62Feno18.6 ± 13.322.4 ± 23.4.52Allergy sensitization33 (73)161 (68).45Asthma symptom days4.3 ± 4.82.9 ± 4.2.03Data presented as No. (%), mean ± SD, or as otherwise noted. National Health and Nutrition Examination Survey (NHANES) III6Hankinson J.L. Odencrantz J.R. Fedan K.B. Spirometric reference values from a sample of the general U.S. population.Am J Respir Crit Care Med. 1999; 159: 179-187Crossref PubMed Scopus (3337) Google Scholar spirometry reference values were used. Asthma symptom days = maximum number of days or nights with asthma symptoms or limited activity because of asthma in the 14 d prior to survey; Feno = fractional exhaled nitric oxide; Premature birth = questionnaire response indicating birth > 3 wk earlier than due date. Open table in a new tab Data presented as No. (%), mean ± SD, or as otherwise noted. National Health and Nutrition Examination Survey (NHANES) III6Hankinson J.L. Odencrantz J.R. Fedan K.B. Spirometric reference values from a sample of the general U.S. population.Am J Respir Crit Care Med. 1999; 159: 179-187Crossref PubMed Scopus (3337) Google Scholar spirometry reference values were used. Asthma symptom days = maximum number of days or nights with asthma symptoms or limited activity because of asthma in the 14 d prior to survey; Feno = fractional exhaled nitric oxide; Premature birth = questionnaire response indicating birth > 3 wk earlier than due date. Children with asthma who are born prematurely may suffer greater asthma morbidity in response to air pollutant exposures. In this analysis, we found that school-aged children with asthma who were born prematurely had a 29% increase in the odds of having an asthma symptom day in response to every 0.1 μg/m3 increase in school classroom BC and worsened lung function with exposure to classroom PM2.5 than term children with asthma. Children born prematurely suffer from a variety of early life pulmonary insults related to insufficient in utero lung development and aggressive resuscitative and supportive treatment in the neonatal period. Previous cohort studies have demonstrated that at school age, preterm children have a higher prevalence of asthma and poorer lung function, while lacking other typical characteristics of childhood asthma.1Halvorsen T. Skadberg B.T. Eide G.E. Roksund O. Aksnes L. Oymar K. Characteristics of asthma and airway hyper-responsiveness after premature birth.Pediatr Allergy Immunol. 2005; 16: 487-494Crossref PubMed Scopus (94) Google Scholar,7Lum S. Kirkby J. Welsh L. Marlow N. Hennessy E. Stocks J. Nature and severity of lung function abnormalities in extremely pre-term children at 11 years of age.Eur Respir J. 2011; 37: 1199-1207Crossref PubMed Scopus (132) Google Scholar The preterm children in this study had similar allergic sensitization and fractional exhaled nitric oxide levels, but did have significantly higher baseline asthma symptom days and lower FVC than term children. Moreover, neonatal events only partially explain school-age respiratory outcomes in preterm children.8Fawke J. Lum S. Kirkby J. et al.Lung function and respiratory symptoms at 11 years in children born extremely preterm: the EPICure study.Am J Respir Crit Care Med. 2010; 182: 237-245Crossref PubMed Scopus (385) Google Scholar It is conceivable that preterm children with asthma have a worse response to known environmental respiratory irritants than term children with asthma because of comorbid lung disease related to prematurity; however, few data exist objectively evaluating post-neonatal ICU events influencing the respiratory health of school-aged children born prematurely. Our findings extend the observation that ambient pollution differentially affects ED visits for preterm children3Strickland M.J. Klein M. Flanders W.D. et al.Modification of the effect of ambient air pollution on pediatric asthma emergency visits: susceptible subpopulations.Epidemiology. 2014; 25: 843-850Crossref PubMed Scopus (40) Google Scholar by detailing the effect of objectively measured personal exposure to pollutants on rigorously collected respiratory health outcomes in preterm children with asthma. Although we did not find a distinct effect on health-care utilization in our study, we confirm the adverse effect of pollutants on asthma symptoms and lung function on preterm children in excess of that of term children. These findings are in concert with a recent report by Collaco et al,9Collaco J.M. Morrow M. Rice J.L. McGrath-Morrow S.A. Impact of road proximity on infants and children with bronchopulmonary dysplasia.Pediatr Pulmonol. 2020; 55: 369-375Crossref PubMed Scopus (11) Google Scholar who found home proximity to roadways associated with symptoms but not health-care utilization in a cohort of patients with bronchopulmonary dysplasia. Our limited sample size and lack of characterization of degree of prematurity may have limited our ability to find other significant associations. Nevertheless, these findings suggest that among inner city school children with asthma, a history of preterm birth is associated with greater asthma symptoms and lower lung function with exposure to in-classroom fine particle pollution. Children born prematurely may be particularly vulnerable to the respiratory effects of air pollution. Further research into the effects of indoor exposures on respiratory health in preterm children is needed. Role of sponsors: The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic health-care centers, or the National Institutes of Health. Its contents are solely the responsibility of the grantee and do not necessarily represent the official views of the USEPA. Furthermore, USEPA does not endorse the purchase of any commercial products or services mentioned in the publication." @default.
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• W3026494485 title "Differential Effect of School-Based Pollution Exposure in Children With Asthma Born Prematurely" @default.
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